IllnessJoubert syndrome, rarely mutated genes; differential diagnosis

JP5550_DH

Joubert syndrome (JS) may affect many parts of the organism, the symptoms vary even among members of the same family. The diagnostic hallmark is a combination of brain abnormalities, shown on MRI as "molar tooth sign," due to abnormal cerebellar vermis and brainstem structures. Most infants with JS present with hypotonia and ataxia along with hyperpnea or apnea and oculomotor apraxia, accompanied by delayed development and mental retardation. Characteristic facial features include broad forehead, arched eyebrows, ptosis, hypertelorism, low-set ears and triangular mouth. The condition is sometimes associated with retinal dystrophy and coloboma, polycystic kidneys and nephronophthisis, liver fibrosis, oral hamartomas, polydactyly or endocrine problems. All cases in which the molar sign occurs are usually considered as JS. They are caused by mutations in at least 34 genes encoding primary cilia proteins and account for >60->90% of JS cases. Pathogenic variants have also been identified in diseases with clinical findings that only overlap with JS. In many cases, it is difficult to determine whether a previously recognized disorder is truly distinct from JS as an allelic disorder or whether it is part of the JS spectrum. JS is usually inherited in an autosomal recessive manner, with rare cases (caused by mutations in one gene) inherited in an X-linked recessive manner. Because the diagnostic yield is not entirely complete, a negative molecular genetic result does not exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1325/

• Allelic: Nephronophthisis 3 (NPHP3)
• Alias: Cerebellooculorenal syndrome
• Alias: Cerebelloparenchymal disorder IV
• Alias: Joubert-Boltshauser syndrome
• Allelic: Acrocallosal syndrome (KIF7)
• Allelic: Basal cell naevus syndrome (SUFU)
• Allelic: Cone-rod dystrophy 20 (POC1B)
• Allelic: Hydrolethalus syndrome 2 (KIF7)
• Allelic: Medulloblastoma, desmoplastic (SUFU)
• Allelic: Meningioma, familial, susceptibility to (SUFU)
• Allelic: Mental retardation, truncal obesity, retinal dystrophy + micropenis (INPP5E)
• Allelic: Nephronophthisis 1, juvenile (NPHP1)
• Allelic: Nephronophthisis 11 (TMEM67)
• Allelic: Nephronophthisis 12 (TTC21B)
• Allelic: Nephronophthisis 14 (ZNF423)
• Allelic: Nephronophthisis 3 (NPHP3)
• Allelic: Retinitis pigmentosa 23 (OFD1)
• Allelic: Retinitis pigmentosa 71 (IFT172)
• Allelic: Short-rib thoracic dysplasia 10 with/-out polydactyly (IFT172)
• Allelic: Short-rib thoracic dysplasia 13 with/-out polydactyly (CEP120)
• Allelic: Short-rib thoracic dysplasia 14 with polydactyly (KIAA0586)
• Allelic: Short-rib thoracic dysplasia 4 with/-out polydactyly (TTC21B)
• Acrocallosal syndrome (KIF7)
• Al-Gazali-Bakalinova syndrome (KIF7)
• Bardet-Biedl syndrome 13 (MKS1)
• Bardet-Biedl syndrome 14, modifier of (TMEM67)
• COACH syndrome 2 (CC2D2A)
• COACH syndrome 3 (RPGRIP1L)
• Cone-rod dystrophy 20 (POC1B)
• Greig cephalopolysyndactyly syndrome (GLI3)
• Hydrolethalus syndrome (HYLS1)
• Hydrolethalus syndrome 2 (KIF7)
• Joubert syndrome 1 (INPP5E)
• Joubert syndrome 10 (OFD1)
• Joubert syndrome 12 (KIF7)
• Joubert syndrome 13 (TCTN1)
• Joubert syndrome 14 (TMEM237)
• Joubert syndrome 15 (CEP41)
• Joubert syndrome 16 (TMEM138)
• Joubert syndrome 17 (C5orf42 syn. CPLANE1)
• Joubert syndrome 18 (TCTN3)
• Joubert syndrome 19 (ZNF423)
• Joubert syndrome 2 (TMEM216)
• Joubert syndrome 20 (TMEM231)
• Joubert syndrome 21 (CSPP1)
• Joubert syndrome 22 (PDE6D)
• Joubert syndrome 23 (KIAA0586)
• Joubert syndrome 24 (TCTN2)
• Joubert syndrome 25 (CEP104)
• Joubert syndrome 26 (KATNIP syn. KIAA0556)
• Joubert syndrome 27 (B9D1)
• Joubert syndrome 28 (MKS1)
• Joubert syndrome 29 (TMEM107)
• Joubert syndrome 30 (ARMC9)
• Joubert syndrome 31 (CEP120)
• Joubert syndrome 32 (SUFU)
• Joubert syndrome 33 (PIBF1)
• Joubert syndrome 34 (B9D2)
• Joubert syndrome 35 (ARL3)
• Joubert syndrome 36 (FAM149B1)
• Joubert syndrome 4 (NPHP1)
• Joubert syndrome 7 (RPGRIP1L)
• Joubert syndrome 8 (ARL13B)
• Joubert syndrome 9 (CC2D2A)
• Meckel syndrome 1 (MKS1)
• Meckel syndrome 10 (B9D2)
• Meckel syndrome 11 (TMEM231)
• Meckel syndrome 13 (TMEM107)
• Meckel syndrome 2 (TMEM216)
• Meckel syndrome 5 (RPGRIP1L)
• Meckel syndrome 6 (CC2D2A)
• Meckel syndrome 7 (NPHP3)
• Meckel syndrome 8 (TCTN2)
• Meckel syndrome 9 (B9D1)
• Orofaciodigital syndrome I (OFD1)
• Orofaciodigital syndrome IV (TCTN3)
• Orofaciodigital syndrome VI (C5orf42 syn. CPLANE1)
• Orofaciodigital syndrome XIV (C2CD3)
• Orofaciodigital syndrome XV (KIAA0753)
• Orofaciodigital syndrome XVI (TMEM107)
• Renal-hepatic-pancreatic dysplasia 1 (NPHP3)
• Retinitis pigmentosa 71 (IFT172)
• Retinitis pigmentosa 83 (ARL3)
• Senior-Loken syndrome (POC1B)
• Senior-Loken syndrome-1 (NPHP1)
• Simpson-Golabi-Behmel syndrome, type 2 (OFD1)